Aberrant brain network connectivity in presymptomatic and manifest Huntington's disease: A systematic review

Lorenzo Pini, Charlotte Jacquemot, Annachiara Cagnin, Francesca Meneghello, Carlo Semenza, Dante Mantini, Antonino Vallesi

Research output: Contribution to journalReview articlepeer-review


Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to shed light on the pathophysiological mechanisms of Huntington's disease (HD), paving the way to new therapeutic interventions. A systematic literature review was conducted in three online databases according to PRISMA guidelines, using keywords for HD, functional connectivity, and rs-fMRI. We included studies investigating connectivity in presymptomatic (pre-HD) and manifest HD gene carriers compared to healthy controls, implementing seed-based connectivity, independent component analysis, regional property, and graph analysis approaches. Visual network showed reduced connectivity in manifest HD, while network/areas underpinning motor functions were consistently altered in both manifest HD and pre-HD, showing disease stage-dependent changes. Cognitive networks underlying executive and attentional functions showed divergent anterior–posterior alterations, possibly reflecting compensatory mechanisms. The involvement of these networks in pre-HD is still unclear. In conclusion, aberrant connectivity of the sensory-motor network is observed in the early stage of HD while, as pathology spreads, other networks might be affected, such as the visual and executive/attentional networks. Moreover, sensory-motor and executive networks exhibit hyper- and hypo-connectivity patterns following different spatiotemporal trajectories. These findings could potentially help to implement future huntingtin-lowering interventions.

Original languageEnglish
JournalHuman Brain Mapping
Publication statusAccepted/In press - Jan 1 2019


  • functional connectivity
  • Huntington's disease
  • resting state networks
  • systematic review

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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